Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.

ABSTRACT: Recent crystallographic structures of G protein-coupled receptors (GPCRs) have greatly advanced our understanding of the recognition of their diverse agonist and antagonist ligands. We illustrate here how this applies to A2A adenosine receptors (ARs) and to P2Y1 and P2Y12 receptors (P2YRs) for ADP. These X-ray structures have impacted the medicinal chemistry aimed at discovering new ligands for these two receptor families, including receptors that have not yet been crystallized but are closely related to the known structures. In this Chapter, we discuss recent structure-based drug design projects that led to the discovery of: (a) novel A3AR agonists based on a highly rigidified (N)-methanocarba scaffold for the treatment of chronic neuropathic pain and other conditions, (b) fluorescent pro

SUBMITTER: Ciancetta A 

PROVIDER: S-EPMC5859332 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature